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Ann Epidemiol. 2004 Jul;14(6):416-24.

Synergism between smoking and vital exhaustion in the risk of ischemic stroke: evidence from the ARIC study.

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  • 1Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL 33612, USA.



To examine the synergism between vital exhaustion and cigarette smoking in producing ischemic stroke. Vital exhaustion (VE), a state characterized by unusual fatigue, irritability, and feelings of demoralization, is measured by the Maastricht questionnaire (MQ), a 21-item inventory of symptoms.


The Atherosclerosis Risk in Communities (ARIC) Study is an ongoing cohort study, initiated in 1987. The MQ was administered at the second follow-up visit (1990-1992), and participants were subsequently followed for an average of 6.27 years. Four US communities (Minneapolis, Minnesota; Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). 13,066 participants aged 48 to 67 years at baseline (Visit 2) with no history of stroke. Validated hospitalized ischemic stroke.


During the follow-up period, there were 202 incident ischemic strokes. After multivariate adjustment, current smoking, and high VE were independent risk factors for incident stroke: (smoking vs. non-smoking HR=1.76, p < 0.01; high VE vs. low VE HR=1.94, p < 0.01). For persons with both VE and smoking vs. persons with neither, HR=2.71 (p < 0.001). The proportion of stroke disease burden due to VE and smoking that could be attributed to their interaction was 81 to 93 percent.


The combination of cigarette smoking and VE is synergistic in the production of stroke.

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